The long term goal of the proposed project is to elucidate through conformational studies the mechanism whereby antithrombin III and heparin affect blood coagulation. Although conformational changes have been proposed for the antithrombin III-thrombin-Heparin interactions, very little direct experimental evidence is available. Specifically, the objectives of this project will be to combine circular dichroism, difference spectroscopy and chemical modification to elucidate: (a) the conformational aspects of the antithrombin III-thrombin reaction in the presence and absence of heparin; (b) to determine the role of the functional groups of heparin in its ability to induce conformational changes in antithrombin III, in particular, and in proteins, in general; and (c) to extend this study on Factor IXa and Factor Xa.